As external preparations containing indomethacin, those of various preparation forms such as a gel formulation, a cream formulation, a liquid formulation, and a poultice formulation are commercially available and those preparations have respective characteristics inherent to the preparation forms.
For example, gel formulations contain a large amount of alcohol so that they dissolve indomethacin well therein and exhibit excellent absorbability through a skin. However, when in use, they cause irregularities (a phenomenon in which a polymer collects like grime when the polymer is coated by rubbing) so that the formulations provide a poor use feeling. On the other hand, cream formulations are blended with a sufficient amount of oil so that after they are used, they do not stick, giving an excellent use feeling. However, because of insufficient solubility of indomethacin therein, the cream formulations exhibit poor absorbability of indomethacin through a skin as compared with that of the gel formulations.
Accordingly, it has been desired to develop a so-called gel-cream formulation that has advantages of both a gel formulation and of a cream formulation, i.e., a satisfactory use feeling and satisfactory absorbability of indomethacin through a skin and for this purpose many studies have been made.
Usually, a surfactant is compounded in a cream formulation in order to prevent phase separation, i.e., separation into an oil layer and an aqueous layer. However, compounding a large amount of alcohol to a cream formulation results in the phase separation of the preparation into an oil layer and an aqueous layer with time since the alcohol inhibits the emulsifying action of the surfactant. In addition, compounding a gelling agent to a cream formulation in such an amount that irregularities will not occur can hardly prevent such phase separation of the preparation with time.
There have been known some prior art documents that report gel-cream formulations containing indomethacin, for example, JP 58-185514 A, JP 59-227818 A, JP 57-126414 A, and JP 1-279831 A. However, the preparation disclosed in JP 58-185514 A has an alcohol content of 10 wt % or less, so that the solubility and percutaneous absorbability of indomethacin are poor. The preparations disclosed in the other prior art documents are unsatisfactory since they cause irregularities specific to gel formulations or phase separation of the preparations.
In view of those drawbacks, it has been demanded to provide an indomethacin external preparation that has an excellent use feeling and excellent absorbability of indomethacin and that undergoes no phase separation of the preparation with time so that it can well retain a stable state.